Prenatal arsenic metabolite exposure is associated with increased newborn mitochondrial DNA copy number: evidence from a birth cohort study.

While mitochondria are susceptible to environmental detriments, little is known about potential associations between arsenic metabolites and mitochondria DNA copy number (mtDNAcn). We attempted to examine whether maternal urinary arsenic metabolite levels in different trimesters were related to neonatal cord blood mtDNAcn. We included 819 mother-newborn pairs embedded in an in-progress birth cohort survey performed from April 2014 to October 2016 in Wuhan, China. We determined maternal urinary arsenic species concentrations in different trimesters. We determined cord blood mtDNAcn using quantitative real-time polymerase chain reaction. In covariate-adjusted models, each one-unit increment of dimethylated arsenic (DMA) and total arsenic (TAs) in the third trimester was related to 8.43% (95% CI 1.13%, 16.26%) and 12.15% (95% CI 4.35%, 20.53%) increases in mtDNAcn, respectively. The dose-response trend with statistical significance was observed across tertiles of DMA and TAs in the third trimester with mtDNAcn (DMA percent changes (%Δ) = 25.60 (95% CI 6.73, 47.82), for the highest vs the lowest tertile (P = 0.02); TAs %Δ = 40.31 (95% CI 19.25, 65.10), for the highest vs the lowest tertile (P = 0.0002)). These findings may prove the relationships between prenatal arsenic species levels and neonatal mitochondrial dysfunction.

Associations between maternal urinary rare earth elements during pregnancy and birth weight-for-gestational age: Roles of cord blood vitamin D levels.

Prenatal exposure to rare earth elements (REEs) may contribute to adverse birth outcomes in previous studies. Cord blood vitamin D has been suggested to modify or mediate the effects of environmental exposures. However, none has investigated these roles of cord blood vitamin D in the associations of prenatal exposure to REEs with fetal growth. Maternal trimester-specific urinary concentrations of 13 REEs, cord blood total 25-hydroxyvitamin D at delivery, and birth weight (BW)-for-gestational age (GA) were determined in 710 mother-newborn pairs from Wuhan, China. Higher maternal average urinary concentrations of europium (Eu), gadolinium (Gd), dysprosium (Dy), holmium (Ho), erbium (Er), and ytterbium (Yb) across three trimesters, either individually or jointly, were significantly associated with lower BW-for-GA Z-scores and higher odds of small for gestational age (SGA) [ß = -0.092; 95 % confidence interval (CI): -0.149, -0.035 for BW-for-GA Z-scores, and odds ratio = 1.60; 95 % CI: 1.14, 2.24 for SGA involved in each unit increase in weighted quantile sum index of REEs mixture]. When stratified by cord blood vitamin D levels, the associations mentioned above persisted in participants with relatively low vitamin D levels (<13.94 µg/L, the first tertile of distribution), but not among those with relatively high levels (≥13.94 µg/L) (all p-values for interaction < 0.05). The mediation analyses taking account of exposure-mediator interaction showed that the relationships between REEs (as individual and mixture) exposure and lower BW-for-GA were partly mediated through decreasing cord blood vitamin D levels. The proportions mediated by cord blood vitamin D levels were 24.48 % for BW-for-GA Z-scores and 29.05 % for SGA corresponding to the REEs mixture exposure. Conclusively, our study revealed that prenatal exposures to Eu, Gd, Dy, Ho, Er, and Yb were related to fetal growth restriction. Cord blood vitamin D might alleviate toxic effects of these REEs and its reduction might partly mediate REE-induced fetal growth restriction.

Urinary biomarkers of exposure to organophosphate, pyrethroid, neonicotinoid insecticides and oxidative stress: A repeated measurement analysis among pregnant women.

Exposure to insecticides may be associated with increased oxidative stress (OS), but few studies have assessed the associations of OS biomarkers (OSBs) with exposure to multiple insecticides and their mixture, especially in pregnant women who are a vulnerable population. In the present study, 1,094 Chinese pregnant women were recruited and a total of 3,282 urine samples were collected at their three trimesters to measure eight metabolites of organophosphates, three metabolites of pyrethroids, nine typical neonicotinoids/their metabolites, and three OSBs of DNA damage (8-OHdG), RNA damage (8-OHG), and lipid peroxidation (HNE-MA). Among the twenty target insecticide metabolites, sixteen of them were frequently detected; thirteen of them were detected in over 86% of all the urine samples except for imidacloprid (IMI, detection frequency: 72.9%), desnitro-imidacloprid (DN-IMI, 70.0%), and clothianidin (CLO, 79.6%). The reproducibility of their concentrations across the three trimesters was poor to fair (intraclass correlation coefficients <0.50). Multiparity and warm season were related to higher urinary levels of some insecticide metabolites, while higher education level and inadequate weight gain during pregnancy were significantly associated with lower concentrations of certain insecticide metabolites. Linear mixed model analyses suggested that almost all the frequently detected insecticide metabolites [other than 3-phenoxybenzoic acid (3-PBA)] were significantly associated with elevated levels of the three OSBs (8-OHdG, 8-OHG, and HNE-MA), where the percent change (Δ%) ranged 8.10-36.0% for 8-OHdG, 8.49-34.7% for 8-OHG, and 5.92-182% for HNE-MA, respectively, with each interquartile ratio (IQR)-fold increase in the concentrations of the individual exposure biomarkers. Weighted quantile sum models demonstrated that the insecticide metabolite mixture was positively associated with the three OSBs. Overall, urinary desmethyl-clothianidin (DM-CLO) and 3,5,6-trichloro-2-pyridinol (TCPy) were the top insecticide exposure biomarkers contributing to the association with 8-OHdG and 8-OHG levels, while PNP contributed the most to the association with HNE-MA levels. These findings suggested that gestational exposure to organophosphates, pyrethroids, neonicotinoids, their transformation products, and their mixture may increase oxidative damage to lipids, RNA, and DNA during pregnancy.

Altered cord blood mitochondrial DNA content and prenatal exposure to arsenic metabolites in low-arsenic areas.

While mitochondria are susceptible to environmental detriments, little is known about potential associations between arsenic metabolites and mitochondria DNA copy number (mtDNAcn). We attempted to examine whether arsenic metabolism in different trimesters was related to cord blood mtDNAcn alteration. We included 819 mother-newborn pairs embedded in an in-progress birth cohort survey performed from April 2014 to October 2016 in Wuhan, China. We determined maternal urinary arsenic species concentrations in different trimesters using HPLC-ICPMS. We decided on cord blood mtDNAcn using quantitative real-time polymerase chain reaction. In covariate-adjusted models, each two-fold increment of dimethylated arsenic (DMA) and total arsenic (TAs) in the 3rd trimester were related to 8.43% (95% CI: 1.13%, 16.26%) and 12.15% (95% CI:4.35%, 20.53%) increases in mtDNAcn, respectively. The dose-response trend with statistical significance was observed across tertiles of DMA and TAs in the 3rd trimester with mtDNAcn. These findings may prove the relationships between arsenic species and mitochondrial dysfunction.

Associations of Trimester-Specific Exposure to Perchlorate, Thiocyanate, and Nitrate with Childhood Neurodevelopment: A Birth Cohort Study in China.

Studies about the impacts of maternal exposure to perchlorate, thiocyanate, and nitrate on offspring neurodevelopment are scarce. Based on a birth cohort in China, 1,028 mothers provided urine samples at three trimesters for determination of the three target analytes, and their offspring neurodevelopment was evaluated at 2 years old. Associations of maternal exposure to the three chemicals with offspring neurodevelopment were estimated using three statistical methods. Trimester-specific analyses using generalized estimating equation models showed that double increment of thiocyanate and nitrate during the first trimester was associated with 1.56 (95% CI: -2.82, -0.30) and 1.22 (-2.40, -0.03) point decreases in the offspring mental development index (MDI), respectively. Weighted quantile sum (WQS) regression analyses showed that the mixture exposure at the first and second trimesters was negatively associated with the offspring MDI (ß = -2.39, 95% CI: -3.85, -0.93; ß = -1.75, 95% CI: -3.04, -0.47, respectively) and thiocyanate contributed the most to the association (65.0 and 91.6%, respectively). Bayesian kernel machine regression analyses suggested an inverted U-shape relationship of maternal urinary thiocyanate with the offspring MDI. These findings suggested that prenatal exposure to the three chemicals (at current levels), especially thiocyanate and nitrate, may impair neurodevelopment. Early pregnancy seems to be the sensitive window.

Prenatal Lead Exposure, Genetic Factors, and Cognitive Developmental Delay.

Importance: Although the effects of lead (Pb) exposure on neurocognition in children have been confirmed, the individual associations of prenatal Pb exposure and its interaction with genetic factors on cognitive developmental delay (CDD) in children remain unclear. Objective: To investigate the association of prenatal Pb exposure and its interaction with genetic factors with CDD risk. Design, Setting, and Participants: Women in Wuhan, China, who had an expected delivery date between March 2014 and December 2017, were recruited for this prospective cohort study. Children were assessed for cognitive development at approximately 2 years of age (March 2016 to December 2019). Maternal venous blood, cord blood, and venous blood from children were collected in a longitudinal follow-up. Data analysis was performed from March 2022 to February 2023. Exposure: Prenatal Pb exposure, and genetic risk for cognitive ability evaluated by polygenic risk score constructed with 58 genetic variations. Main Outcomes and Measures: Cognitive developmental delay of children aged approximately 2 years was assessed using the Chinese revision of the Bayley Scale of Infant Development. A series of multivariable logistic regressions was estimated to determine associations between prenatal Pb exposure and CDD among children with various genetic backgrounds, adjusting for confounding variables. Results: This analysis included 2361 eligible mother-child pairs (1240 boys [52.5%] and 1121 girls [47.5%]; mean [SD] ages of mothers and children, 28.9 [3.6] years and 24.8 [1.0] months, respectively), with 292 children (12.4%) having CDD. Higher maternal Pb levels were significantly associated with increased risk of CDD (highest vs lowest tertile: odds ratio, 1.55; 95% CI, 1.13-2.13), adjusting for demographic confounders. The association of CDD with maternal Pb levels was more evident among children with higher genetic risk (highest vs lowest tertile: odds ratio, 2.59; 95% CI, 1.48-4.55), adjusting for demographic confounders. Conclusions and Relevance: In this cohort study, prenatal Pb exposure was associated with an increased risk of CDD in children, especially in those with a high genetic risk. These findings suggest that prenatal Pb exposure and genetic background may jointly contribute to an increased risk of CDD for children and indicate the possibility for an integrated strategy to assess CDD risk and improve children's cognitive ability.

Associations of plasma manganese with adverse pregnancy outcomes: Nested case-control studies in a Chinese birth cohort.

Both insufficient and excessive manganese exposure are associated with adverse pregnancy outcomes. However, no systematic research has established a standardized reference range for manganese levels with the consideration of the associated health risks during pregnancy. To verify the associations of prenatal manganese exposure with adverse outcomes and to identify a proper reference range for manganese based on health risks, we designed three nested case-control studies on three adverse outcomes including hypertensive disorders of pregnancy (HDP), preterm birth (PTB), and low birth weight (LBW) to investigate the associations with manganese levels. Plasma manganese concentrations in early pregnancy were measured. Conditional logistic regression analyses were used to estimate the associations of manganese levels with adverse outcomes. Restricted cubic spline (RCS) models were used to characterize the dose-response relationship of manganese and each outcome. Nonlinear associations were observed for manganese and adverse outcomes. Compared with women in the middle tertile of plasma manganese, we found that those in the highest tertile had a significantly higher risk of HDP (OR = 1.72, 95% CI: 1.02 to 2.89), that women in the lowest tertile had almost a tripled risk of delivering LBW infants (OR = 2.93, 95% CI: 1.67 to 5.17), and that women both in the lowest and the highest tertiles had significantly higher risks of PTB [OR = 1.83 (95% CI: 1.14 to 2.95); OR = 1.70 (95% CI: 1.05 to 2.76)]. U-shaped associations were found between plasma manganese and risk of PTB and infant LBW. Based on the results of RCS models, we identified a proper plasma manganese range of 1.72-3.18 µg/L, with relatively lower risks of adverse pregnancy outcomes. In conclusion, our study found U-shaped associations between manganese exposure and adverse pregnancy outcomes, and provided an optimal range of manganese concentration for pregnant women, based on health risk considerations.

Urinary perchlorate, thiocyanate, and nitrate and their associated risk factors among Chinese pregnant women.

Perchlorate, nitrate, and thiocyanate are well-known inhibitors of iodide uptake and thyroid-disrupting chemicals. Widespread human exposure to them has been identified, whereas studies on their internal exposure levels among Chinese pregnant women are scarce and factors associated with them are not well recognized. The objective of this study is to determine their levels and identify the associated factors among pregnant women (n = 1120), based on a prospective birth cohort in Wuhan, central China, using repeated urine samples of three trimesters. Urinary perchlorate, thiocyanate, and nitrate were 100% detected in the samples, and specific gravity-adjusted median concentrations of them in all the samples were 12.6 ng/mL, 367 ng/mL, and 63.7 µg/mL, respectively. Their concentrations were weakly-to-moderately correlated with each other, with Spearman correlation coefficients ranging from 0.27 to 0.54. Poor reproducibility were observed for the three analytes over the three trimesters, with intraclass correlation coefficient of 0.07, 0.19, 0.04 for perchlorate, thiocyanate, and nitrate, respectively. The women who were overweight or used tap water as drinking water had significantly higher perchlorate concentrations, while those with excessive gestational weight gain had significantly higher thiocyanate concentrations (p < 0.05). The women with a college degree or above had lower nitrate concentrations (p < 0.05). Meanwhile, the median concentration of perchlorate in urine samples collected in spring, thiocyanate in those collected in winter, and nitrate in those collected in autumn, was significantly higher compared to their median concentrations in the samples collected in other three seasons (p < 0.05), respectively. Urinary perchlorate and nitrate concentrations of pregnant women in this study were higher than the concentrations of pregnant women in other countries, while thiocyanate concentrations were lower than that of most other countries. This study suggested potential covariates for future epidemiological analyses.

Prenatal arsenic exposure, arsenic metabolism and neurocognitive development of 2-year-old children in low-arsenic areas.

BACKGROUND: There is limited evidence on the effects of arsenic species and metabolic capacity on child neurodevelopment, particularly at low levels. Further, little is known about the critical window of exposure. OBJECTIVE: To estimate the associations of arsenic exposure and arsenic metabolism in different pregnancy periods with neurodevelopment of two-year-old children. METHODS: Concentrations of arsenobetaine (AsB), arsenite, arsenate, monomethyl arsenic acid (MMA), and dimethyl arsenic acid (DMA) in urine samples collected in three trimesters from 1006 mothers were measured using HPLC - ICPMS. Inorganic arsenic (iAs) was calculated as the sum of arsenite and arsenate. Total arsenic (tAs) was calculated as the sum of iAs, MMA and DMA. Child neurodevelopment was assessed with the Bayley Scales of Infant Development. RESULTS: The geometric mean (GM) of SG-adjusted tAs in the first, second, third trimester was 16.37, 12.94, 13.04 µg/L, respectively. The mental development index (MDI) score was inversely associated with iAs and tAs. Compared to the 1st quartile, the MDI score decreased 0.43 (95%CI: -4.22, 3.36) for the 2nd, 6.50 (95%CI: -11.73, -1.27) for the 3rd, 5.42 (95%CI: -10.74, -0.10) for the 4th quartiles of iAs, and decreased 4.03 (95%CI: -7.90, -0.15) in the 4th quartile of tAs. In trimester-specific models, negative associations of DMA [-1.94 (95%CI: -3.18, -0.71)] and tAs [-1.61 (95%CI: -3.02, -0.20)] with the psychomotor development index (PDI) were only observed in 1st trimester. CONCLUSIONS: Our study found inverse associations between prenatal arsenic exposure, especially in early pregnancy, and neurodevelopment of children at two years old, even at low exposure levels.

Association of arsenic exposure and clinical hematological changes during pregnancy: Findings from a prospective Wuhan birth cohort study.

BACKGROUND: Animal studies have reported arsenic-induced disturbed erythropoiesis parameters. However, the effects of exposure to arsenic on hematological parameters among pregnant women are unclear. OBJECTIVES: We aimed to evaluate trimester-specific associations between arsenic metabolites and erythropoietic parameters measured repeatedly during pregnancy. METHODS: A total of 1945 pregnant women from a birth cohort study were included. We detected arsenic species in urine sampled at each trimester and extracted erythropoietic parameters in different trimesters from the medical records. We used linear regressions with generalized estimating equations (GEEs) to examine the relationship between arsenic metabolites concentrations at different trimesters and erythropoietic parameters. We utilized GEEs to calculate the odds ratio (OR) for anemia during pregnancy. RESULTS: Adjusted trimester-specific analysis showed that higher monomethylated arsenic (MMA) and %MMA were related to remarkably reduced hemoglobin (Hb) and mean corpuscular hemoglobin (MCH). Additionally, elevated urinary MMA concentration and %MMA in the early trimester were associated with an increased risk of microcytic anemias in the late trimester. CONCLUSIONS: Our study demonstrated a significant inverse relationship between gestational arsenic exposure and Hb and MCH. Notably, higher MMA and lower methylation capacity to metabolize inorganic arsenic (iAs) in early pregnancy might increase the likelihood of microcytic anemia among pregnant women in late pregnancy.

Associations of arsenic exposure with blood pressure and platelet indices in pregnant women: A cross-sectional study in Wuhan, China.

BACKGROUND: Environmental inorganic arsenic (iAs) exposure is potentially related to abnormal blood pressure (BP) changes and abnormal platelet activation. However, limited epidemiological studies have explored the impacts of iAs exposure on platelet change mediated by BP, especially for pregnant women. OBJECTIVES: Our purpose was to investigate the associations of arsenic exposure with blood pressure and platelet indices among pregnant women. METHODS: The present study population included 765 pregnant women drawn from a prospective birth cohort study in Wuhan, China, recruited between October 2013 and April 2016. Urine sampled in the second trimester were used to assess arsenic species concentrations. The relative distribution of urinary arsenic species was used to measure human methylation capacity. BP parameters and platelet indices originated from the medical record. We applied multivariable linear regression models to explore the cross-sectional relationships between urinary arsenic metabolites, BP parameters, and platelet indices. We utilized mediation analysis to investigate the impacts of arsenic exposure on platelet indices through BP as mediator variables. RESULTS: We observed significant positive correlations between iAs and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Pregnant women with higher methylation capacity to metabolize iAs characterized by higher secondary methylation index (SMI) and total methylation index (TMI) had a more significant reduction in SBP, DBP, and MAP. Pregnant women with higher DBP and MAP had higher platelet counts (PLC). A decreased PLC was found in subjects wither higher SMI. Additionally, SMI was negatively linked to PLC mediated through MAP. CONCLUSIONS: Obtained results suggested that higher methylation capacity to metabolize iAs might contribute to decreased PLC among pregnant women, and MAP might mediate the influence of SMI on PLC.

Genetic determinants for the racial disparities in the risk of prostate and testicular cancers.

BACKGROUND: A worldwide higher incidence of prostate cancer and lower incidence of testicular cancer in men of African ancestry compared to European ancestry has been observed previously. However, underlying mechanisms accounting for these observations are largely unknown. METHODS: The current study analyzed previously reported SNPs associated with either prostate cancer or testicular cancer to examine whether the risk allele frequency could help us understand the observed incidence disparities in men of African ancestry and European ancestry. Both t-test and regression analysis were performed. RESULTS: Here we show that men of African ancestry are more likely to have risk alleles of prostate cancer and less likely to have risk alleles of testicular cancer compared to men of European ancestry. CONCLUSIONS: Our findings suggest that genetic factors may play an important role in the racial disparities in the risk of prostate and testicular cancers.

It has been observed that men of African ancestry have a higher incidence of prostate cancer and lower incidence of testicular cancer compared to men of European ancestry. However, little is known about underlying mechanisms accounting for these observations. The current study compares frequencies of all genetic alterations associated with risks of prostate cancer or testicular cancer between the two racial groups. Our findings suggest that differences in the frequencies of genetic alterations between the groups may help to explain the racial disparities in the risk of prostate and testicular cancers.

Association of exposure to per- and polyfluoroalkyl substances with hemoglobin and hematocrit during pregnancy.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are common environmental contaminants and are widely detected in humans. Previous studies have linked PFASs exposure to adverse birth outcomes. However, the association between maternal exposure to PFASs and hemoglobin (Hb) and hematocrit (HCT) remains unclear. OBJECTIVES: We aimed to explore the relationship between PFASs exposure with Hb and HCT during pregnancy. METHODS: The present birth cohort study included 1044 pregnant women from Wuhan, China. Maternal HCT and Hb were measured in the first, second and third trimesters, and 13 PFASs were detected in the cord sera. Mixed linear models and general linear regression were applied to analyze the association between each single PFASs and Hb and HCT. Weighted quantile sum (WQS) regressions were used to investigate the association between PFASs mixture and Hb and HCT during pregnancy. RESULTS: In single-PFAS models, 10 PFASs were positively associated with HCT and Hb across pregnancy (a 10-fold increase in PFASs was associated with 1.47-3.54 % change in HCT and 1.46-3.20 % change in Hb (All P-FDR < 0.05). In addition, Hb and HCT were more positively related to PFASs in the second and third trimesters rather than the first trimester. The association between PFASs exposure and maternal HCT and Hb was not significant in the iron supplementation group, whereas significant in the non-iron supplementation group. A significant interaction between iron supplementation and non-iron supplementation was also detected. WQS regressions showed that perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS) contributed most to the association between PFASs and HCT and Hb in the second and third trimesters, respectively. CONCLUSION: Maternal PFASs exposure was positive with serum Hb and HCT. Moreover, maternal iron supplementation may play a modifying effect in influencing the relationship between PFASs and HCT and Hb.

Association between maternal family history of hypertension and preterm birth: modification by noise exposure and multivitamin intake.

OBJECTIVE: To measure the effect of maternal family history of hypertension on preterm birth (PTB) and to identify factors that modified this association. METHODS: A case-control study was nested in a prospective cohort of the entire pregnant population in Wuhan, China, from 2011 to 2013. Home-visit interviews were scheduled for all PTBs and their controls, to collect extensive information on maternal exposures to behavioral, environmental, and intergenerational risk factors of PTB. The effects of maternal family history of hypertension on PTB were measured by logistic regression analyses, controlling for potential confounders. Potential effect modifiers were examined using stratified analyses. RESULTS: There were 2393 PTBs and 4263 full-term births out of all eligible births. A positive association was observed between maternal family history of hypertension and PTB, after adjusted for potential confounders (adjusted odds ratio: 1.17 [1.03, 1.33]). A higher effect was observed when mothers were exposed to certain noise during pregnancy (adjusted odds ratio: 1.37 [1.14, 1.65]) and/or when they did not take multivitamins during pregnancy (adjusted odds ratio: 1.46 [1.20, 1.78]), whereas, this association was weaker and no longer significant when mothers took multivitamins during pregnancy (adjusted odds ratio: 1.00 [0.84, 1.19]) and/or when they were not exposed to certain noise during pregnancy (adjusted odds ratio: 1.01 [0.85, 1.12]). The modification effect from maternal multivitamin intake was significant on both spontaneous and medically indicated PTBs, and the modification effect from maternal exposure to certain noise was only significant on spontaneous PTB. CONCLUSIONS: Increased PTB risk was observed for pregnant women with a family history of hypertension in Wuhan, China. This effect was stronger when pregnant women did not take multivitamin and/or exposed to certain noise during pregnancy, than those who took multivitamin and/or unexposed to certain noise.

Urinary paracetamol (4-acetaminophenol) and its isomer 2-acetaminophenol of Chinese pregnant women: Exposure characteristics and association with oxidative stress biomarkers.

N-Acetyl-4-aminophenol (NA4AP, paracetamol/acetaminophen), a widely used pharmaceutical, is ubiquitous in urine samples of general population, raising concern about human health risks; oxidative stress is considered to be a mechanism for its toxicities. N-Acetyl-2-aminophenol (NA2AP) is an isomer of NA4AP; until now, few studies characterized exposure characteristics of NA4AP and NA2AP in pregnant women. In this work, NA4AP and NA2AP concentrations in urine samples (n = 2124) collected at three different trimesters were measured to examine their internal body burden among Chinese pregnant women (n = 708) and their associations with three oxidative stress biomarkers (OSBs, 8-OHG, 8-OHdG, and HNE-MA). NA4AP was detected in 100% of the urine samples (median concentration: 7.96 ng/mL); NA2AP was detected in 94.9% of them (median: 3.05 ng/mL). The intraclass correlation coefficients of their concentrations across three trimesters were poor (<0.4); correlations of NA4AP and NA2AP were weak (r: 0.15-0.23). Pregnant women who had higher household income or urine samples provided in summer (vs. winter) had higher concentrations of NA4AP. Pregnant women who had a college degree or above (vs. less than a high school education) had higher concentrations of NA2AP but urine samples provided in summer (vs. winter) had lower concentrations of NA2AP. The 95th percentile estimated daily intake of NA4AP (2,331 ng/kg-bw/d) based on averaged concentrations of the three trimesters was 40 times lower than the cRfD for NA4AP (2.33 vs. 93 µg/kg-bw/d). Urinary concentrations of NA4AP and NA2AP were associated with higher levels of the selected OSBs. For example, an interquartile range increase in NA4AP was associated with a 26.5% (95% CI: 23.6-29.6%) increase in 8-OHG, a 27.5% (95% CI: 23.8-31.3%) increase in 8-OHdG, and a 33.4% (95% CI: 24.7-42.7%) increase in HNE-MA (p < 0.05). This is the first study to measure their concentrations repeatedly over three trimesters, examine their exposure characteristics, and reveal their associations with the selected OSBs in pregnant women. Further studies are needed to identify non-intentional exposure sources of NA4AP, NA2AP, and another isomer of them (i.e., N-acetyl-3-aminophenol), as well as more health risks related to their exposure.

Fish intake and risk of melanoma in the NIH-AARP diet and health study.

PURPOSE: Prior epidemiological studies evaluating the association between fish intake and melanoma risk have been few and inconsistent. Few studies distinguished different types of fish intake with risk of melanoma. METHODS: We examined the associations between intake of total fish and specific types of fish and risk of melanoma among 491,367 participants in the NIH-AARP Diet and Health Study. We used multivariable-adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 6,611,941 person-years of follow-up with a median of 15.5 years, 5,034 cases of malignant melanoma and 3,284 cases of melanoma in situ were identified. There was a positive association between higher total fish intake and risk of malignant melanoma (HR = 1.22, 95% CI = 1.11-1.34 for top vs. bottom quintiles, ptrend = 0.001) and melanoma in situ (HR = 1.28, CI = 1.13-1.44 for top vs. bottom quintiles, ptrend = 0.002). The positive associations were consistent across several demographic and lifestyle factors. There were also positive associations between tuna intake and non-fried fish intake, and risk of malignant melanoma and melanoma in situ. However, fried fish intake was inversely associated with risk of malignant melanoma, but not melanoma in situ. CONCLUSIONS: We found that higher total fish intake, tuna intake, and non-fried fish intake were positively associated with risk of both malignant melanoma and melanoma in situ. Future studies are needed to investigate the potential biological mechanisms underlying these associations.

Cold chain and severe acute respiratory syndrome coronavirus 2 transmission: a review for challenges and coping strategies.

Since June 2020, the re-emergence of coronavirus disease 2019 (COVID-19) epidemics in parts of China was linked to the cold chain, which attracted extensive attention and heated discussions from the public. According to the typical characteristics of these epidemics, we speculated a possible route of transmission from cold chain to human. A series of factors in the supply chain contributed to the epidemics if the cold chain were contaminated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as temperature, humidity, personal hygiene/protection, and disinfection. The workers who worked in the cold chain at the receiving end faced a higher risk of being infected when they were not well protected. Facing the difficult situation, China put forward targeted and powerful countermeasures to block the cold chain-related risk. However, in the context of the unstable pandemic situation globally, the risk of the cold chain needs to be recognized and evaluated seriously. Hence, in this review, we reviewed the cold chain-related epidemics in China, analyzed the possible mechanisms, introduced the Chinese experience, and suggested coping strategies for the global epidemic prevention and control.

Association Study between Polymorphisms in DNA Methylation-Related Genes and Testicular Germ Cell Tumor Risk.

BACKGROUND: Testicular germ cell tumors (TGCT), histologically classified as seminomas and nonseminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when they are subjected to DNA methylation reprogramming. SNPs in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation. METHODS: In this pathway-focused investigation, we evaluated the association between 273 selected tag SNPs from 28 DNA methylation-related genes and TGCT risk. We carried out association analysis at individual SNP and gene-based level using summary statistics from the Genome Wide Association Study meta-analysis recently conducted by the international Testicular Cancer Consortium on 10,156 TGCT cases and 179,683 controls. RESULTS: In individual SNP analyses, seven SNPs, four mapping within MTHFR, were associated with TGCT risk after correction for multiple testing (q ≤ 0.05). Queries of public databases showed that three of these SNPs were associated with MTHFR changes in enzymatic activity (rs1801133) or expression level in testis tissue (rs12121543, rs1476413). Gene-based analyses revealed MTHFR (q = 8.4 × 10-4), methyl-CpG-binding protein 2 (MECP2; q = 2 × 10-3), and ZBTB4 (q = 0.03) as the top TGCT-associated genes. Stratifying by tumor histology, four MTHFR SNPs were associated with seminoma. In gene-based analysis MTHFR was associated with risk of seminoma (q = 2.8 × 10-4), but not with nonseminomatous tumors (q = 0.22). CONCLUSIONS: Genetic variants within MTHFR, potentially having an impact on the DNA methylation pattern, are associated with TGCT risk. IMPACT: This finding suggests that TGCT pathogenesis could be associated with the folate cycle status, and this relation could be partly due to hereditary factors.

Urinary paraben derivatives in pregnant women at three trimesters: Variability, predictors, and association with oxidative stress biomarkers.

Exposure to parabens has been shown to increase oxidative stress, which has a vital impact on the development of numerous diseases. However, few studies reported the effects of the paraben derivatives on oxidative stress, particularly among pregnant women. This study, using repeated measurements, aimed to understand the exposure profiles of urinary paraben derivative concentrations and their relationships with oxidative stress biomarkers (OSBs). A total of 861 pregnant women, who provided spot urine samples at three trimesters, were included, and 2583 urine samples were used to measure four paraben derivatives [p-hydroxybenzoic acid (p-HB), 3,4-dihydroxybenzoic acid (3,4-DHB), methyl protocatechuate, and ethyl protocatechuate], four parabens (methyl, ethyl, propyl, and butyl), and three OSBs [8-hydroxy-2'-deoxyguanosine (for DNA), 8-hydroxyguanosine (for RNA), and 4-hydroxy nonenal mercapturic acid (for lipid)]. Pregnant women were extensively exposed to parabens and paraben derivatives with detection frequencies (DFs) of 86.1%-100%, except for butylparaben with a DF of 14.9%. p-HB and 3,4-DHB had relatively high urinary concentrations (specific gravity-adjusted median values: 1394 and 74.5 ng/mL, respectively). Low reproducibility in paraben derivatives was found across the three trimesters. Sampling season, pre-pregnancy body mass index, and infant sex were predictors of some paraben derivatives/parabens. Linear mixed model analyses showed that all target compounds (if DF > 50%) were associated with increases in all the selected OSBs, where the percent change in OSBs with an interquartile range increase in paraben concentration ranged from 9.85% to 24.7%, while those in paraben derivative concentration ranged from 13.8% to 72.1%. Weighted quantile sum model showed that joint exposure was significantly associated with increased OSBs, and paraben derivatives were stronger contributors to OSBs compared with parabens. Overall, urinary paraben derivatives were associated with increased oxidative stress of nucleic acids and lipid in pregnant women.